VITAMIN-E AMELIORATES ENHANCED RENAL LIPID-PEROXIDATION AND ACCUMULATION OF F-2-ISOPROSTANES IN AGING KIDNEYS

Aging results in progressive glomerular sclerosis and reductions in gl omerular filtration rate (GFR). Oxidative stress may be an important m echanism for the aging process, but to date the role of oxidative stre ss on renal aging has not been determined. The present study was perfo rmed to determine whether age-related alterations in renal hemodynamic s and morphology were associated with oxidative stress and whether thi s could be attenuated by chronic administration of vitamin E. Rats, ag ed 13 mo, were given either control diet containing vitamin E 50 IU/kg (n = 6) or a high-vitamin E diet (5,000 IU/kg; n = 6) for 9 mo. Anoth er group of rats (3-4 mo old; n = 7) served as young controls. Aging w as accompanied by a 60% reduction in GFR, a threefold increase in rena l F-2 isoprostanes, newly discovered vasoconstrictive F-2-like prostag landins generated by free radical-mediated lipid peroxidation. Renal a ging was also associated with an increase in oxidant-sensitive heme ox ygenase, advanced glycosylation end products (AGEs), and the AGE recep tor, RAGE. AGE-RAGE interaction has been shown to induce oxidative str ess. With high-vitamin E diet, GFR was increased by 50%, F-2 isoprosta nes were suppressed, and expression of heme oxygenase and RAGE was att enuated. There was also a tendency for glomerular sclerosis to be atte nuated. These data demonstrate that age-related decline in renal funct ion is accompanied by oxidative stress and that administration of anti oxidants, such as vitamin E, could attenuate the decline in renal func tion.